Bioinformatics education course on gene networks reconstruction using online tools

Bioinformatics education requires the use of online computer tools for modeling protein-protein interactions, visual presentation of the networks, access to open databases. The usage of online bioinformatics tools makes it possible to reconstruct both protein and genes networks, and develop modeling skills for students. We consider the issues of computer reconstruction of gene networks - complexes of interacting macromolecules - using a list of genes associated with a particular disease, or a complex disorder based on public online bioinformatics tools - STRINGDB, GeneMANIA, Metascape, Cytoscape applications. Examples of computer reconstruction and visualization of gene networks of oncological diseases including glioma, breast cancer, as well as complex mental disorders such as Parkinson’s disease, schizophrenia, were recently published in co-authorship with the students. The use of only online bioinformatics tools is educational in nature, focused on students, both in mathematics and in natural sciences and medical disciplines, who do not have enough skills in computer science, programming, and writing their own code. Automatic construction of lists of genes associated with a disease using open databases (OMIM, GeneCards, MalaCards), computer reconstruction of gene networks, calculations of enrichment statistics for gene ontology categories have been successfully mastered by students. The educational bioinformatics materials designed for the students and with the students were tested at several universities in Russia, including courses in English for foreign students studied in Russia. The tasks of digitalization of medicine, the development of IT technologies are in the priority. The epidemic situation that has existed in recent years and the forced transition to distance learning had accelerated the adoption of measures to change the formats of education, the emergence of new learning platforms. Note a number of qualitatively new tasks of education in the field of digital healthcare, such as the use of blockchain technologies, the use of Artificial Intelligence (AI) methods in support of medical decision-making. Overall, the educational course developed includes a theoretical part (video lessons) and a practical part - performing tasks on the use of computer programs and databases that have found a number of applications for medical problems in the reconstruction and analysis of networks of interactions of macromolecules.Book of abstract: 4th Belgrade Bioinformatics Conference, June 19-23, 202

Negative high-frequency differential conductivity in semiconductor superlattices

We examine the high-frequency differential conductivity response properties of semiconductor superlattices having various miniband dispersion laws. Our analysis shows that the anharmonicity of Bloch oscillations (beyond tight-binding approximation) leads to the occurrence of negative high-frequency differential conductivity at frequency multiples of the Bloch frequency. This effect can arise even in regions of positive static differential conductivity. The influence of strong electron scattering by optic phonons is analyzed. We propose an optimal superlattice miniband dispersion law to achieve high-frequency field amplification

Dysfunction in Ribosomal Gene Expression in the Hypothalamus and Hippocampus following Chronic Social Defeat Stress in Male Mice as Revealed by RNA-Seq

Chronic social defeat stress leads to the development of anxiety-and depression-like states in male mice and is accompanied by numerous molecular changes in brain. The influence of 21-day period of social stress on ribosomal gene expression in five brain regions was studied using the RNA-Seq database. Most Rps, Rpl, Mprs, and Mprl genes were upregulated in the hypothalamus and downregulated in the hippocampus, which may indicate ribosomal dysfunction following chronic social defeat stress. There were no differentially expressed ribosomal genes in the ventral tegmental area, midbrain raphe nuclei, or striatum. This approach may be used to identify a pharmacological treatment of ribosome biogenesis abnormalities in the brain of patients with "ribosomopathies.&quot

Entropy Analysis of Protein Sequences Reveals a Hierarchical Organization

Background: Analyzing the local sequence content in proteins, earlier we found that amino acid residue frequencies differ on various distances between amino acid positions in the sequence, assuming the existence of structural units. Methods: We used informational entropy of protein sequences to find that the structural unit of proteins is a block of adjacent amino acid residues—“information unit”. The ANIS (ANalysis of Informational Structure) method uses these information units for revealing hierarchically organized Elements of the Information Structure (ELIS) in amino acid sequences. Results: The developed mathematical apparatus gives stable results on the structural unit description even with a significant variation in the parameters. The optimal length of the information unit is five, and the number of allowed substitutions is one. Examples of the application of the method for the design of protein molecules, intermolecular interactions analysis, and the study of the mechanisms of functioning of protein molecular machines are given. Conclusions: ANIS method makes it possible not only to analyze native proteins but also to design artificial polypeptide chains with a given spatial organization and, possibly, function

Self-induced and induced transparencies of two-dimensional and three- dimensional superlattices

The phenomenon of transparency in two-dimensional and three-dimensional superlattices is analyzed on the basis of the Boltzmann equation with a collision term encompassing three distinct scattering mechanisms (elastic, inelastic and electron-electron) in terms of three corresponding distinct relaxation times. On this basis, we show that electron heating in the plane perpendicular to the current direction drastically changes the conditions for the occurrence of self-induced transparency in the superlattice. In particular, it leads to an additional modulation of the current amplitudes excited by an applied biharmonic electric field with harmonic components polarized in orthogonal directions. Furthermore, we show that self-induced transparency and dynamic localization are different phenomena with different physical origins, displaced in time from each other, and, in general, they arise at different electric fields.Comment: to appear in Physical Review

Integrative analysis of the human cis-antisense gene pairs, miRNAs and their transcription regulation patterns

Cis-antisense gene pairs (CASGPs) can transcribe mRNAs from an opposite strand of a given locus. To classify and understand diverse CASGP phenomena in the human we compiled a genome-wide catalog of CASGPs and integrated these sequences with microarray, SAGE and miRNA data. Using the concept of overlapping regions and clustering of SA transcripts by chromosome coordinates, we identified up to 9000 overlapping antisense loci. Four thousand three hundred and seventy-four of these CASGPs form 1759 complex gene architectures. We found that ∼35% (6347/18160) of RefSeq genes are overlapped with the antisense transcripts. About 30% of Affymetrix U133 microarray initial sequences map transcripts of ∼35% CASGPs and reveal mostly concordant expression in CASGPs. We found strong significant overrepresentation of human miRNA genes in loci of CASGPs. We developed a data-driven model of cross-talk between co-expressed CASGPs and DICER1-mediated miRNA pathway in normal spermatogenesis and in severe teratozoospermia. Specifically, we revealed complex SA structural–functional gene module composing the protein-coding genes, WDR6, DALRD3, NDUFAF3 and ncRNA precursors, mir-425 and mir-191, which could provide downregulation of ncRNA pathway via direct targeting DICER1 and basonuclin 2 transcripts by mir-425 and mir-191 in normal spermatogenesis, but this mechanism is switched off in severe teratozoospermia. The database is available from http://globalisland.bii.a-star.edu.sg/∼jiangtao/sas/index3.php?link =abou

Extensive Promoter-Centered Chromatin Interactions Provide a Topological Basis for Transcription Regulation

Higher-order chromosomal organization for transcription regulation is poorly understood in eukaryotes. Using genome-wide Chromatin Interaction Analysis with Paired-End-Tag sequencing (ChIAPET), we mapped long-range chromatin interactions associated with RNA polymerase II in human cells and uncovered widespread promoter-centered intragenic, extragenic, and intergenic interactions. These interactions further aggregated into higher-order clusters, wherein proximal and distal genes were engaged through promoter-promoter interactions. Most genes with promoter-promoter interactions were active and transcribed cooperatively, and some interacting promoters could influence each other implying combinatorial complexity of transcriptional controls. Comparative analyses of different cell lines showed that cell-specific chromatin interactions could provide structural frameworks for cell-specific transcription, and suggested significant enrichment of enhancer-promoter interactions for cell-specific functions. Furthermore, genetically-identified disease-associated noncoding elements were found to be spatially engaged with corresponding genes through long-range interactions. Overall, our study provides insights into transcription regulation by three-dimensional chromatin interactions for both housekeeping and cell-specific genes in human cells